Asymmetric MPV reduction

An intriguing chiral samarium complex for the Meerwein-Pondorf-Verley (MPV) reduction of ketones has been reported by Evans.100 The soluble catalyst, prepared as indicated in Figure 46, promoted the asymmetric MPV reduction of aryl methyl ketones in up to 97% ee with as little as 5 mol % loading (Figure 47). 

Other selected examples are summarized in Table 2. In addition to aldehydes, both cyclic and acyclic ketones can be reduced equally well. sec-Phenethyl alcohol (11, R = Ph) as hydride source works more effectively than t-PrOH. On the basis of this finding, the asymmetric MPV reduction of unsymmetrical ketones with chiral alcohol in the presence of catalyst 10 was examined [30]. Treatment of 2-chloroacetophenone (12) with optically pure (R)-(+)-sec-phenethyl alcohol (1 equiv.) under the influence of catalytic 10 at 0 °C for 10 h afforded (5)-(+)-2-chloro-l-phenylethanol (13) with moderate asymmetric induction (82 %, 54 % enantiomeric excess, ee Sch. 8). Switch-... 

An asymmetric MPV reduction that uses i-PrOH, MCjAl, and a chiral bi-naphfhol has also been reported [169]. (P)-BINOL and Me Al were mixed in a 1 1 ratio in toluene and the resulting white precipitate was treated with a prochiral ketone (tenfold excess) and i-PrOH (40-fold excess) (Scheme 6.129). This simple method was found to effect the catalytic reduction of 2-chloroacetophenone at r.l. to give the alcohol in 80% ee and 99% yield. 

The Maruoka group developed asymmetric MPV allq nylations catalysed by the axially chiral biphenol ligands derived catalyst 46 (Scheme 19.55), and the corresponding alcohols were obtained in 64-96% enantiomeric excess. Very recently, Nandi, Katz and coworkers reported an Al-calix[4]arene-catalyst 47 for the asymmetric MPV reduction (Scheme 19.56). The most enantioselective catalyst consisted of a new axially chiral vaulted-hemispherical calyx[4]arene phosphite ligand, which delivered the chiral alcohols with enantiomeric excesses up to 99%. 

Scheme 19.56 Asymmetric MPV reductions catalysed by Al-calix[4]arene catalyst.

A tandem 1,4-addition-Meerwein-Ponndorf-Verley (MPV) reduction allows the reduction of a, /i-unsaturated ketones with excellent ee and in good yield using a camphor-based thiol as reductant.274 The 1,4-addition is reversible and the high ee stems from the subsequent 1,7-hydride shift the overall process is thus one of dynamic kinetic resolution. A crossover experiment demonstrated that the shift is intramolecular. Subsequent reductive desulfurization yielded fiilly saturated compounds in an impressive overall asymmetric reductive technique with apparently wide general applicability. 

A new type of lanthanoid complex, prepared from BINOL and SmCl3, served as an asymmetric catalyst for MPV reduction of aryl methyl ketones in the presence of molecular sieves. Moderate enantioselectivity was obtained.101... 

Asymmetric reduction of ketones by means of this MPV reduction was also tested (Scheme 6.128). The reduction proceeded with substoichiometric amounts of optically pure a-phenethylalcohol to give the product secondary alcohol in a moderate yield with fairly high ee of 82% [167]. 

Asymmetric MPV type reduction can be achieved by using a chiral Sm(III) complex 38 (Scheme 29) [93]. Several aryl methyl ketones are reduced in an excellent optical yield, up to 97%. Electronic properties of substrates profoundly affect the reactivity. For example, a p-chloro substituent in the benzene ring accelerates the reaction, whereas a p-methoxy substituent decelerates the reduction. The presence of an o-chloro or o-methoxy group effectively enhances the... 

Asymmetric, borane-modified MPV reduction of a variety of aromatic ketones to their corresponding alcohols has recently (43) been reported using a chiral aluminum alkoxide catalyst shown in Figure 5. This compound was formed in situ from aluminum isopropoxide and (R)-l,r-binapthyl-diol in... 

Scheme 7.35 Asymmetric Meerwein-Ponndorf-Varley (MPV) reduction under flow conditions.

Apart from the Meerwin-Ponndorf-Verley (MPV) reaction,16 18catalytic asymmetric transfer hydrogenation has remained quite primitive,111,112 with successful examples of reduction of activated olefins, using alcohols or formic acid as hydrogen source, being reported only recently.113,114... 

Modified MPV-type reductions carried out with chiral magnesium alkoxides and with chiral Grignard reagents have been discussed in detail (1). These reagents differ from the aluminum alkoxides since the Grignard reaction is essentially irreversible. Chiral alkali metal alkoxides have also been used to effect asymmetric reductions (1). 

The asymmetric reduction of prochiral ketones to their corresponding enantiomerically enriched alcohols is one of the most important molecular transformations in synthetic chemistry (20,21). The products are versatile intermediates for the synthesis of pharmaceuticals, biologically active compounds and fine chemicals (22,23). The racemic reversible reduction of carbonyls to carbinols with superstoichiometric amounts of aluminium alkoxides in alcohols was independently discovered by Meerwein, Ponndorf and Verley (MPV) in 1925 (21—26). Only in the early 1990s, first successful versions of catalytic... 

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